Healthcare in India

Healthcare in India

Guidelines on Prevention, Diagnosis and Treatment of Infective Endocarditis


Infective Endocarditis (IE) is a fatal disease if it remains untreated. Early signs of IE are fever or septicaemia and cardiac murmurs.Previous history of IE, presence of prosthetic heart valves or other foreign material, surgically created conduits, and complex cyanotic congenital abnormalities are considered high risk conditions. Other high risk non-cardiac situations include older age, promotion of non-bacterial thrombotic vegetation, compromised host defense and increased risk/frequency/amount of bacteraemia. Involvement of endocardium during a systemic infection establishes IE Dental hygiene is of significance in prevention of IE Prophylactic use of antibiotics is a class I recommendation. Penicillin G is effective treatment. For penicillin resistant strains vancomycin plus gentamycin are effective. Management of Native and Prosthetic Valve Endocarditis is achieved by surgical means and postoperative antibiotic treatment regardless of the duration of treatment prior to surgery.
If untreated, Infective Endocarditis (IE) is a fatal disease. Major diagnostic (first of all echocardiography) and therapeutic progress (mainly surgery during active IE) have contributed to some prognostic improvement during the last decades. If the diagnosis is delayed or appropriate therapeutic measures postponed, mortality is still high. In this respect, it is of utmost importance that:-

  • IE is considered early in every patient with fever or septicaemia and cardiac murmurs.
  • Echocardiography is applied without delay in suspected IE
  • Cardiologists, microbiologists and cardiac surgeons should cooperate closely if IE is suspected or definite.

Definitions
IE is an endovascular, microbial infection of intracardiac structures facing the blood including infections of the large intrathoracic vessels and of intracardiac foreign bodies. The early characteristic lesion is variably sized vegetation, although destruction, ulceration or abscess formation may be seen earlier by echocardiography.

Prevention of Infective Endocarditis
For prophylactic reasons, antibiotics should be given before a bacteraemia is expected. If antibiotic prophylaxis is not given prior to this event, antibiotics may help a late clearance if administered intravenously within 23h.

Cardiac conditions/patients at risk for IE
A previous history of IE, the presence of prosthetic heart valves or otherforeign material, surgically created conduits, and complex cyanotic congenital abnormalities are considered high-risk situations. Only patients with high or moderate risk should receive prophylaxis. This is a class I recommendation based on level C evidence.
Patient-related non-cardiac conditions
Older age, conditions (a), promoting non-bacterial thrombotic vegetation; (b), compromising host defense; (c), compromising local non-immune defence mechanisms; and (d), increased risk/frequency/amount of bacteraemia are considered patient related, non-cardiac risk conditions.

Predisposing diagnostic and therapeutic interventions
Procedures which may cause bacteraemia and for which antimicrobial prophylaxis is recommended are given in. Prophylaxis is not recommended for cardiac catheterization. Dental hygiene is of major importance for the prevention of IE.
Prophylactic Antibiotic Regimens
Prophylaxis aims primarily at viridans streptococci and HACEK organisms before dental, oral, respiratory, and oesophageal procedures, and at enterococci and Streptococcus bovis before gastrointestinal and genitourinary procedures. Despite a lack of convincing evidence, antibiotic prophylaxis is a class I recommendation (based on level C evidence).
Diagnosis
History, symptoms, signs and laboratory tests
The diagnosis of IE is established (definite IE) if during a systemic infection involvement of the endocardium is demonstrated. If, in addition, bacteraemia (positive blood cultures) or bacterial DNA are found, IE is definite and culture/microbiologically positive, otherwise IE is definite but culture/microbiologically negative. Duke or modified Duke criteria may be used to make the diagnosis in otherwise unclear cases.


Echocardiography
Any patient suspected of having NVE by clinical criteria should be screened by transthoracic echocardiography (TTE). When images are of good quality and prove to be negative and there is only a low clinical suspicion of IE, endocarditis is unlikely and other diagnoses are to be considered. If suspicion of IE is high, transoesophageal echocardiography (TEE) should be performed in all TTE-negative cases, in suspected PVE and if TTE is positive but complications are suspected or likely and before cardiac surgery during active IE. If TEE remains negative and there is still suspicion, it should be repeated within one week. A repeatedly negative study should virtually exclude the diagnosis. These class I recommendations are based on level B evidence.


Three echocardiographic findings are considered to be major criteria in the diagnosis of IE: (a), a mobile, echodense mass attached to the valvular or the mural endocardium or to implanted prosthetic material; (b), demonstration of abscesses or fistulas; (c), a new dehiscence of a valve prosthesis, especially when occurring late after implantation.


Standard blood culture techniques
Three or more blood cultures (BC) should be taken irrespective of body temperature at least 1h apart. If the patient has been on short-term antibiotics, one should wait, if possible, at least for three days after discontinuing antibiotic treatment before new BCs are taken. Blood cultures after long-term antibiotic treatment may not become positive after treatment has been discontinued for 67 days.
One BC consists of one aerobic and one anaerobic bottle, each containing approx. 50ml of medium (less in pediatric BC bottles). Venous blood, minimally 5ml and better 10ml in adults and 15ml in children should be added to each bottle. Minimum inhibitory concentrations should be determined for the drugs of choice.


Culture-negative endocarditis (CNE)
The most frequent cause of CNE is previous antimicrobial treatment. If traditional (non-automatic) BC systems are used, longer incubation periods (>6 days) are required when organisms of the HACEK group, Propionibacterium spp., Neisseria spp., Brucella, Abiotrophia spp., or Campylobacter spp. are suspected. Especially in CNE all material excised during cardiac surgery for active IE should also be cultured and examined.


The value of serology has been proven for IE due to Bartonella, Legionella, Chlamydia (immunofluorescence) and Coxiella burnetii.
The use of broad-spectrum polymerase chain reaction (PCR) provides a significant improvement in the capability to detect difficult-to-culture organisms and even dead bacteria.

Treatment and Management

  • Antimicrobial therapy

a Especially for patients allergic to penicillin

  • 23mg/kg netilmicin once daily may be an alternative (peak serum level <16mg/l).
  • High level resistance (HLR) to penicillin or ceftriaxone (MIC >8mg/l) and HLR to gentamicin (MIC >500mg/l) or resistance to vancomycin or teicoplanin (MIC ?4mg/l) are rare among strains of streptococci. In such situations, extended susceptibility testing and a close cooperation with the clinical microbiologist are mandatory.
  • For resistant enterococci treatment with oxazolidinone may be an option but should be initiated only after advice from a reference centre has been taken.
  • a Methicillin-susceptible S. aureus.
  • b Or its congeners.
  • c Except for drug addicts for whom a 2-week regimen may be sufficient (see chapters 5.6.3 of the full version of this guideline).
  • d For both, immediate (IgE) type and hypersensitivity reaction during treatment.
  • e Infusion over at least 60min.
  • f Total treatment duration for patients initially treated with oxacillin should be at least 4 weeks. These patients should not have a second course of gentamicin treatment.
  • g Methicillin-resistant S. aureus.
  • h Coagulase-negative staphylococci. In oxacillin-susceptible CONS vancomycin should be replaced by oxacillin.
  • i For resistant staphylococci treatment with oxazolidinone may be an option but should be initiated only after advice from a reference centre has been taken.
  • j If gentamicin susceptibility has been shown in vitro, gentamicin is added in MRSA for the full course but for CONS only for the first 2 weeks of treatment. If the organism is resistant to all aminoglycosides, gentamicin may be substituted by a fluoroquinolone.
  • a Maximum 2g/day; for drug level monitoring see below and full guideline text.
  • b Aminopenicillin may be added.

All patients with streptococcal IE should be treated for at least 2 weeks in hospital and observed for cardiac and non-cardiac complications. Patients may then be candidates for outpatient and home parenteral antibiotic therapy. Treatment recommendations for streptococcal IE are based on consistent results of a large number of studies (class I recommendation based on level B evidence).
IE caused by methicillin-resistant S. aureus (MRSA) is a therapeutic challenge as most strains are also resistant to most aminoglycosides. If the clinical course is complicated, treatment should be as for PVE.

Coagulase-negative species (CONS) causing PVE within the first year after valve replacement are usually methicillin-resistant. Therapy of choice is a combination of vancomycin and rifampicin for at least 6 weeks with the addition of gentamicin for the initial 2 weeks.
Despite lack of randomized studies and level A evidence, the scientific material available is convincing and allows for a class I recommendation.
Enterococci are generally resistant to a wide range of antimicrobial agents including aminoglycosides (MIC for gentamicin 464mg/l). (Table 6)
Duration of treatment should be at least 4 weeks for the combination and at least 6 weeks in complicated cases, in patients having symptoms for more than 3 months, and in patients with PVE. These class IIa recommendations are based on level B evidence.

  • Drug level monitoring

Gentamicin trough levels should be less than 0.1mg/l to avoid renal or ototoxic effects.
Optimum vancomycin effects are achieved if serum concentrations are continuously kept at least 24 times above the MIC of the causative organism. Trough levels should be at least 1015mg/l. In patients with normal renal function, drug levels should be controlled once, but 23 times weekly if combined with aminoglycosides.

  • Empirical therapy

In cases complicated by sepsis, severe valvular dysfunction, conduction disturbances, or embolic events, empirical antimicrobial therapy should be started after three blood cultures have been taken (see standard blood culture techniques section).
Recommendations for empirical antibiotic treatment (before microbiologic test results are available) and CNE are given in Table 8.

  • Special subsets

Antimicrobial therapy for infections of permanently implanted pacemakers or ICD leads are based on culture and susceptibility results. Duration of therapy should be 46 weeks in most cases. Removal of the entire system is generally recommended.

  • In intravenous drug abusers (IVDAs), a methicillin-susceptible S. aureus (MSSA) is the causative organism in about 6070% of cases. The tricuspid valve is affected in more than 70%.
  • The most common organism (S. aureus) must always be covered by the antibiotic regimen.
  • Treatment will include either penicillinase-resistant penicillins or vancomycin, depending on the local prevalence of MRSA.
  • If the patient is a pentazocine addict, an antipseudomonas agent should be added.
  • If IVDAs use brown heroine dissolved in lemon juice, Candida should be considered and antifungal treatment added.
  • In IVDAs with underlying valve lesions and/or left-sided involvement, antibiotic treatment against streptococci and enterococci must be added.

Management of Complications
Rapid and effective antimicrobial treatment may help to prevent embolism. If the patient is on long-term oral anticoagulation, coumarin therapy should be discontinued and replaced by heparin immediately after thediagnosis of IE has been established.

After an embolic complication, the risk for recurrent episodes is high. After manifestation of a cerebral embolism, cardiac surgery to prevent a recurrent episode is not contraindicated if performed early (best within 72h) and cerebral haemorrhage has been excluded by cranialcomputed tomography immediately before the operation. If surgery is not performed early it is advisable to postpone for 34 weeks.

 Surgery for Active NVE
The following indications for urgent valve surgery are accepted:

  • Heart failure due to acute aortic regurgitation;
  • Heart failure due to acute mitral regurgitation;
  • Persistent fever and demonstration of bacteremia for more than 8 days despite adequate antimicrobial therapy;
  • Demonstration of abscesses, pseudoaneurysms, abnormal communications like fistulas or rupture of one or more valves, conduction disturbances, myocarditis or other findings indicating local spread (locally uncontrolled infection);
  • Involvement of microorganisms which are frequently not cured by antimicrobial therapy (e.g. fungi; Brucella and Coxiella) or microorganisms which have a high potential for rapid destruction of cardiac structures (e.g. S. lugdunensis).

If vegetations are larger than 10mm on the mitral valve or if they are increasing in size despite antibiotic therapy or if they represent mitral kissing vegetations, early surgery should also be considered.

The prognosis of right-sided IE is favourable. Surgery is necessary if tricuspid vegetations are larger than 20mm after recurrent pulmonary emboli.

Surgery for Active PVE
The following indications are accepted:

  • Early PVE (less than 12 months after surgery)
  • Late PVE complicated by prosthesis dysfunction including significant perivalvular leaks or obstruction, persistent positive blood cultures, abscess formation, conduction abnormalities, and large vegetations, particularly if staphylococci are the infecting agents.

Postoperative Antibiotic Treatment
A full course of antimicrobial treatment should be completed regardless of the duration of treatment prior to surgery, but at least 715 days postoperatively.